Fecal Microbiota Transplant Did Not Improve MDRO Decolonization

Key Takeaways

• No significant difference in 4-week MDRO decolonization was observed between FMT and sham.
• Reductions in AMR genes also did not differ significantly, and adverse events were similar across groups.
• FMT increased bacterial diversity and short-chain fatty acid-producing taxa, while virome findings were unchanged and mycobiome shifts were modest and transient.

In a randomized, double-blind, sham-controlled clinical trial, a single fecal microbiota transplant did not improve 4-week MDRO decolonization over sham in patients with gastrointestinal disease and persistent MDRO colonization confirmed after discharge. Decolonization occurred in 18 of 58 patients given FMT and 17 of 56 given sham, an absolute difference of 0.6 percentage points, with a 95% confidence interval from -16.2 to 17.6 percentage points and no significant between-group difference. Participants had underlying gastrointestinal disease, with colonization identified at discharge screening and persistence confirmed on postdischarge retesting. No short-term decolonization advantage was observed with the intervention in this population.

The trial enrolled 114 patients at a tertiary care center in India, including a gastroenterology ward and intensive care unit, and assigned 58 to FMT and 56 to sham. The cohort included 52 patients with pancreatitis, 43 with cirrhosis, and 19 with other gastrointestinal disorders, most colonized with CRE or ESBL-producing Enterobacteriaceae. Eligible participants had persistent MDRO colonization after discharge, had stopped antibiotics for at least 7 days, and underwent fresh FMT by colonoscopy or sham sigmoidoscopy with saline injection. Bowel preparation was standardized, no preprocedural antibiotics or probiotics were used, and the co-primary outcomes were decolonization and reduction in antimicrobial resistance genes at about 4 weeks. Five patients were lost to follow-up, with two in the FMT group and three in the sham group.

In intention-to-treat analyses, neither culture-based decolonization nor change in antimicrobial resistance genes differed significantly between groups. Median PCR-detected genes declined from 3.0 to 2.5 after FMT and from 3.0 to 2.0 after sham, with no significant between-group difference at P=.68. The primary assessment was planned at 4 weeks, although some samples were collected between 4 and 6 weeks. Among 71 patients assessed within 4 to 6 weeks, per-protocol decolonization was 28.9% with FMT and 33.3% with sham, for an absolute difference of -4.4 percentage points. The median interval from intervention to sampling was 35 days, and microbiologic endpoints remained aligned over short-term follow-up.

FMT was associated with increased bacterial diversity and enrichment of short-chain fatty acid–producing taxa, although postintervention diversity measures did not differ significantly from sham. Viral diversity did not change significantly, and fungal community shifts were modest and transient. Adverse events were comparable, with transient diarrhea in two FMT patients and one sham patient, and nausea or vomiting in one patient per group; fever cultures did not yield MDROs. Seven patients developed fever within 4 weeks, eight required antibiotics, no deaths occurred, and one FMT patient developed acute variceal bleeding. The authors noted limited rectal swab culture methods, a restricted AMR-gene panel, a heterogeneous population, and a single-session protocol, keeping applicability bounded to similar patients with gastrointestinal disease and persistent MDRO colonization.